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Gastrointestinal Stromal Tumors (GISTs)Phase 2NCT02889328

Phase II Study of Regorafenib Continuous Dosing of Regorafenib in Patients With GISTs

A Phase 2 study testing Regorafenib in people with Gastrointestinal Stromal Tumors (GISTs), run by Asan Medical Center at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Randomized, placebo-controlled, phase III study of regorafenib 160 mg once daily on intermittent dosing schedule of 3 weeks on treatment followed by 1 weeks off demonstrated the significant benefit of regorafenib in terms of PFS in patients with GISTs who had failed to both imatinib and sunitinib. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Gastrointestinal Stromal Tumors (GISTs)
What is being tested?
Regorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteSouth Korea
Study dates
Sep 2016to Jan 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 20 years or older, at the time of acquisition of informed consent
  • Histologically confirmed metastatic and/or advanced (unresectable or recurrent) GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRα gene
  • Disease progression or intolerance to imatinib as well as disease progression on sunitinib Disease progression is defined as (1) size increase > 20% by RECIST version 1.1, (2) appearance of a definite new lesion (excluding small cystic new lesions in the liver within 6 months of starting TKIs), (3) new solid nodule within a cystic mass, or (4) increase of the size (> 20%) of previously existing solid nodule within a cystic mass. Intolerance to previous TKIs is defined as (1) drug compliance < 75% due to grade 2 or more non-hematologic toxicities despite dose reduction to one dose level below (300 mg per day for imatinib; 37.5 mg per day on a 4 weeks on and 2 weeks off schedule or 25 mg per day continuous dosing for sunitinib), (2) Febrile neutropenia, grade 4 neutropenia for more than 6 days, grade 4 thrombocytopenia, grade 3 thrombocytopenia with clinically significant bleeding, grade 3-4 or continuous intolerable grade 2 non-hematologic toxicities despite dose reduction to one dose level below as described above.
  • ECOG performance status of 0~1
  • Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 4.03
  • At least one measurable lesion as defined by RECIST version 1.1.
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  • Adequate bone marrow, hepatic, renal, and other organ functions
  • Neutrophil > 1,500/mm3
  • Platelet > 100,000/mm3
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Lipase ≤ 1.5 x the ULN
  • AST/ALT < 3.0 x ULN (or < 5 x ULM in case of liver metastases)
  • Alkaline phosphatase (ALP) limit ≤ 2.5 x ULN (≤5 x ULN for patients with liver involvement of their cancer and /or have bone metastases).
  • Estimated creatinine clearance (CLcr) ≥ 30 mL/min as calculated using the Cockcroft-Gault equation.
  • International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g. heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care.
  • Electrolytes should be within normal limits.
  • Urine dipstick reading: Negative for proteinuria or, if documentation of +1 results for protein on dipstick reading, then total urinary protein ≤ 500 mg and measured creatinine clearance ≥ 30 mL/min/1.73m2 from a 24-hour urine collection
  • Life expectancy > 12 weeks
  • Women with reproductive potential must have a negative serum or urine pregnancy test; and men and women of reproductive potential must practice an effective method of avoiding pregnancy while receiving study drug.
  • Provision of a signed written informed consent
  • Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care
  • Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment

Who cannot join

  • Prior use of any VEGFR inhibitor other than sunitinib (e.g., sorafenib)
  • Subjects who have received:
  • -any other approved tyrosine kinase inhibitor within 1 week or a minimum 5 drug half- lives, whichever is longer (i.e., within 7 days for imatinib or within 10 days for sunitinib)
  • any other investigational new drugs within 4 weeks or 5 drug half-lives (if drug half-life in subjects is known), whichever is shorter.
  • Women of child-bearing potential who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.
  • Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
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  • LVEF < 45% as determined by MUGA scan or echocardiogram
  • Complete left bundle branch block
  • Obligate use of a cardiac pacemaker
  • Congenital long QT syndrome
  • History or presence of ventricular tachyarrhythmia
  • Presence of unstable atrial fibrillation (ventricular response > 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria
  • Clinically significant resting bradycardia (< 50 bpm)
  • Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg, with or without anti-hypertensive medication).
  • QTc > 480 msec on screening ECG
  • Right bundle branch block + left anterior hemiblock (bifasicular block)
  • Angina pectoris ≤ 3 months prior to starting study drug
  • Acute Myocardial Infarction ≤ 3 months prior to starting study drug
  • Other clinically significant heart disease (e.g., CHF, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
  • Diabetes mellitus (insulin dependent or independent disease, requiring chronic medication) with signs of clinically significant peripheral vascular disease.
  • Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month.
  • Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, adrenal or thyroid glands.
  • Prior acute or chronic pancreatitis of any etiology.
  • Acute and chronic liver disease and all chronic liver impairment.
  • Malabsorption syndrome or uncontrolled gastrointestinal toxicities (nausea, diarrhea, vomiting) with toxicity greater than NCI CTCAE grade 2.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study.
  • Treatment with any of the medications that have a potential risk of prolonging the QT interval or inducing Torsades de Points and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, rifampin, phenytoin and quinidine 2 weeks prior baseline.
  • Major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy.
  • Known diagnosis of HIV infection (HIV testing is not mandatory).
  • History of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients with brain metastases as assessed by radiologic imaging (e.g. CT, MRI)
  • Alcohol or substance abuse disorder.
  • Non-healing wound, non-healing ulcer, or non-healing bone fracture
  • Patients with evidence or history of any bleeding diathesis, irrespective of severity
  • Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication.
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
  • Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
  • Ongoing infection > Grade 2 NCI CTCAE

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center, University of Ulsan College of Medicine

    Seoul, 138-736

Other trials in South Korea

About this study

Official title: Phase II Study of Continuous Dosing of Regorafenib in Patients With Gastrointestinal Stromal Tumors (GISTs) After Failure of Imatinib and Sunitinib: GIST Regorafenib Continuous Dosing

Randomized, placebo-controlled, phase III study of regorafenib 160 mg once daily on intermittent dosing schedule of 3 weeks on treatment followed by 1 weeks off demonstrated the significant benefit of regorafenib in terms of PFS in patients with GISTs who had failed to both imatinib and sunitinib. However, there are concerns that tumors and tumor-related symptoms may be progressed during off treatment period. Investigators hypothesize that continuous dosing schedule of regorafenib might be feasible and effective to prevent disease flare on off-treatment period. Based on the results of previous dose escalation study for continuous regorafenib dosing, we investigate the 100 mg daily dose of regorafenib in patients with TKI-refractory GISTs.

Being tested
Regorafenib
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02889328
Study groupRoleWhat they receive
regorafenibExperimentalregorafenib 100 mg po od daily, every 4 weeks (28 day)
Receives: Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease control rate

    Disease control rate (CR + PR + SD) lasting for at least 12 weeks according to the RECIST v1.1

    Measured: at least 12 weeks

Secondary outcomes (3)

  1. Progression-free survival

    Measured: up to 2 years

  2. Overall survival

    Measured: up to 2 years

  3. Toxicity profile by the NCI-CTCAE v4.03

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion9 Aug 2017
  4. Study completionJan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02889328
Sponsor's protocol ID
AMC1602
Status last verified
Jan 2020
First submitted
31 Aug 2016
Last updated
9 Jan 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Kim JJ, Ryu MH, Yoo C, Beck MY, Ma JE, Kang YK. Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib. Oncologist. 2019 Nov;24(11):e1212-e1218. doi: 10.1634/theoncologist.2019-0033. Epub 2019 Apr 29.

    PubMed 31036770

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib in people with Gastrointestinal Stromal Tumors (GISTs), run by Asan Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease control rate (time frame: at least 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02889328, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020.

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